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Since the 2005 FDA hearing that resulted in the removal of Vioxx and Bextra from the US market, the safety of nonselective NSAIDs (nsNSAIDs) and selective Cox-2 inhibitors (e.g., celecoxib) has been repeatedly questioned, often without new or substantive data. Cardiologists and rheumatologists disagree over the magnitude of cardiovascular risk and all recognize that the much greater GI risks require careful patient selection for long-term NSAID use. The prospective, 24,000 patient PRECISION trial intends to study the long term safety of celecoxib versus ibuprofen or naproxen, but has been slowly enrolling since 2006 and may not complete until 2016.
The Standard care versus Celecoxib Outcome Trial (SCOT) was presented in a Hot Line session at ESC Congress recently. This large prospecitve trial, included 7297 subjects taking chronic, prescribed NSAIDs in a primary care setting, included osteoarthritis and rheumatoid arthritis patients aged 60 years and more, who were free from known cardiovascular disease. Patients either continue their nsNSAID or switch to celecoxib and were then followed for a median of three years.
The primary endpoint was a cardiovascular composite of non-fatal MI, acute coronary syndrome, non-fatal stroke or cardiovascular death. The secondary outcomes were hospitalisation or death for upper gastrointestinal ulcer complications such as bleeding, perforation or obstruction. The study found no significant differences between groups for any of the outcomes, with the cardiovascular outcome occurring in 1.8 % of the celecoxib group and 2.2% of the nsNSAID group (hazard ratio1.12; P=0.50). Ulcer-related upper gastrointestinal complications were also uncommon in both groups. Investigators noted that the low frequency of these events made it difficult to enroll.
Serious adverse reactions occurred at a similar rate (5.2% in the celecoxib group versus 5.8% in the nsNSAID group), but there were significantly more withdrawals from celecoxib compared to nsNSAID treatment (50.9% versus 30.2%, P< 0.0001) in this 3 year study. Reasons for withdrawal included lack of efficacy, poor tolerability and adverse effects.
The study suggests that celecoxib is as safe as other nsNSAIDs in patients without cardiac disease, but does not address the safety of these drugs in those with cardiac risk factors.